A taste of Tuscany

The purpose of this Honor’s Paper is to demonstrate the comprehensive scholastic work and practical experience that we—Taylor Palma, Jackie Herrick, and Brigid Greaney—have completed in the Hart School of Hospitality, Sport & Recreation Management at James Madison University. In this paper we will discuss our Themed Event project, A Taste of Tuscany, with its rationale rooted in Italian food and wine culture. Authenticity and faithfulness to the Italian ways were of chief importance throughout the planning and execution of our project. In outlining the details of our event, we have included the logistics, from menus to floor diagrams, as well as personal reflections. Moreover, our learning experience extended well beyond the formal classroom walls and into the realm of applied theory. In turn, our Honors College project synthesizes the educational experiences we have gathered throughout our experiential learning journey

Exploring the Potential Role of Family History of Hypertension on Racial Differences in Sympathetic Vascular Transduction

The prevalence of hypertension in Non-Hispanic Black (BL) men surpasses all other racial groups. Our laboratory has previously demonstrated exaggerated vasoconstrictor and blood pressure (BP) responses to spontaneous bursts of muscle sympathetic nerve activity (MSNA; sympathetic vascular transduction) in young, healthy BL men compared to their Non-Hispanic White (WH) counterparts. Because a family history of hypertension (FHH) further compounds cardiovascular risk, we wanted to begin to explore the potential impact of a positive (+) FHH on sympathetic vascular transduction. Whether a +FHH influences sympathetic vascular transduction in WH and/or BL men remains unknown. PURPOSE: To begin to explore if +FHH influences sympathetic vascular transduction within and between racial groups. METHODS: 22 men, nine with a +FHH (4 BL men) and 13 without a FHH (-FHH; 6 BL men) were recruited. Beat-to-beat BP (Finometer), femoral artery blood flow (Doppler ultrasound), and MSNA were measured during a 20-minute quiet rest. The mean BP and leg vascular conductance (LVC; blood flow/mean BP) responses to spontaneous bursts of MSNA were quantified via a signal averaging technique. RESULTS: Resting heart rate, BP, and MSNA were not significantly different between groups (all p\u3e0.05). As previously demonstrated by our laboratory, the BL men exhibited an augmented sympathetic vascular transduction compared to the WH men (e.g., peak BP response, WH men: Δ4.1±0.3, BL men: Δ5.6±0.7 mmHg, p=0.04). When accounting for FHH within the groups, the peak BP (WH +FHH: Δ4.4±0.6 vs. WH -FHH: Δ3.8±0.4 mmHg, p=0.4) and nadir LVC responses (WH +FHH: Δ-0.5±0.07 vs. WH -FHH: Δ-0.5±0.09 ml·min-¹·mmHg-¹, p=0.7) were not significantly different between WH men +FHH and WH men –FHH. Likewise, the BL men +FHH exhibited similar peak BP (BL +FHH: Δ6.2±0.7 vs. BL -FHH: Δ5.3±1.1 mmHg, p=0.5) and nadir LVC (BL +FHH: Δ-1.1±0.44 vs. BL -FHH: Δ-0.6±0.10 ml·min-¹·mmHg-¹, p=0.2) responses to bursts of MSNA compared to the BL men –FHH. CONCLUSION: These preliminary findings do not support a role for +FHH in augmented sympathetic vascular transduction, therefore suggesting that racial differences in sympathetic vascular transduction are independent of FHH

Quantum fluctuations of D5dD_{5d} polarons on C60C_{60} molecules

The dynamic Jahn-Teller splitting of the six equivalent $D_{5d}$ polarons due to quantum fluctuations is studied in the framework of the Bogoliubov-de Gennes formalism. The tunneling induced level splittings are determined to be $^2 T_{1u} \bigoplus ^2 T_{2u}$ and $^1 A_g \bigoplus ^1 H_g$ for $C_{60}^{1-}$ and $C_{60}^{2-}$, respectively, which should give rise to observable effects in experiments.Comment: REVTEX 3.0, 13 pages, to be published in Phys. Rev.

Mutational escape from the polyclonal antibody response to SARS-CoV-2 infection is largely shaped by a single class of antibodies

Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasma, including plasma from individuals from whom some of the antibodies were isolated. The plasma-escape maps most closely resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is dominated by a single class of antibodies targeting an epitope that is already undergoing rapid evolution

Metal-induced assembly of a semiconductor-island lattice: Getruncated pyramids on Au-patterned Si

We report the two-dimensional alignment of semiconductor islands using rudimentary metal patterning to control nucleation and growth. In the Ge on Si system, a square array of sub-micron Au dots on the Si (001) surface induces the assembly of deposited Ge adatoms into an extensive island lattice. Remarkably, these highly ordered Ge islands form between the patterned Au dots and are characterized by a unique truncated pyramidal shape. A model based on patterned diffusion barriers explains the observed ordering and establishes general criteria for the broader applicability of such a directed assembly process to quantum dot ordering

SARS-CoV-2 variants, spike mutations and immune escape.

Although most mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about 11 months. Since late 2020, however, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations, in the context of 'variants of concern', that impact virus characteristics, including transmissibility and antigenicity, probably in response to the changing immune profile of the human population. There is emerging evidence of reduced neutralization of some SARS-CoV-2 variants by postvaccination serum; however, a greater understanding of correlates of protection is required to evaluate how this may impact vaccine effectiveness. Nonetheless, manufacturers are preparing platforms for a possible update of vaccine sequences, and it is crucial that surveillance of genetic and antigenic changes in the global virus population is done alongside experiments to elucidate the phenotypic impacts of mutations. In this Review, we summarize the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets

Abundant Fas expression by gastrointestinal stromal tumours may serve as a therapeutic target for MegaFasL

Although the tyrosine kinase inhibitor imatinib has been shown to be an active agent in patients with gastrointestinal stromal tumours (GIST), complete remissions are almost never seen and most patients finally experience disease progression during their course of treatment. An alternative therapeutic option is to target death receptors such as Fas. We showed that a panel of imatinib-sensitive (GIST882) and imatinib-resistant (GIST48, GIST430 and GIST430K-) cell lines expressed Fas. MegaFasL, a recently developed hexameric form of soluble Fas ligand (FasL), appeared to be an active apoptosis-inducing agent in these cell lines. Moreover, MegaFasL potentiated the apoptotic effects of imatinib. Immunohistochemical evaluations, in 45 primary GISTs, underscored the relevance of the Fas pathway: Fas was expressed in all GISTs and was expressed strongly in 93%, whereas FasL was expressed at moderate and strong levels in 35 and 53% of GISTs, respectively. Fas and FasL expression were positively correlated in these primary GISTs, but there was no association between Fas or FasL expression and primary site, histological subtype, tumour size, mitotic index, risk classification, and KIT mutation status. The abundant immunohistochemical Fas and FasL expression were corroborated by western blot analysis. In conclusion, our data implicate Fas as a potential therapeutic target in GIST

Selection analysis identifies unusual clustered mutational changes in Omicron lineage BA.1 that likely impact Spike function.

Among the 30 non-synonymous nucleotide substitutions in the Omicron S-gene are 13 that have only rarely been seen in other SARS-CoV-2 sequences. These mutations cluster within three functionally important regions of the S-gene at sites that will likely impact (i) interactions between subunits of the Spike trimer and the predisposition of subunits to shift from down to up configurations, (ii) interactions of Spike with ACE2 receptors, and (iii) the priming of Spike for membrane fusion. We show here that, based on both the rarity of these 13 mutations in intrapatient sequencing reads and patterns of selection at the codon sites where the mutations occur in SARS-CoV-2 and related sarbecoviruses, prior to the emergence of Omicron the mutations would have been predicted to decrease the fitness of any genomes within which they occurred. We further propose that the mutations in each of the three clusters therefore cooperatively interact to both mitigate their individual fitness costs, and adaptively alter the function of Spike. Given the evident epidemic growth advantages of Omicron over all previously known SARS-CoV-2 lineages, it is crucial to determine both how such complex and highly adaptive mutation constellations were assembled within the Omicron S-gene, and why, despite unprecedented global genomic surveillance efforts, the early stages of this assembly process went completely undetected